Stage IV Pancreatic Cancer Patient Treated With FOLFIRINOX Combined With Oral Methioninase: A Highly-Rare Case With Long-term Stable Disease

Kubota, Yutaro; Han, Qinghong; Hozumi, Chihiro; Masaki, Noriyuki; Yamamoto, Jun; Aoki, Yusuke; Tsunoda, Takuya; Hoffman, Robert M.

doi:10.21873/anticanres.15734

Cited by 21 publications

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“…rMETase alone or at combination with chemotherapy has been shown to be active clinically with major cancer types (20)(21)(22)(23)(24). Synergy of methionine restriction and chemotherapy was discovered by our team (25) and is called the Hoffman protocol, which targets methionine addiction which is the fundamental chracteristic of cancer (13,(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Oral-recombinant Methioninase in Combination With Rapamycin Eradicates Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model

Masaki¹,

Han²,

Samonte³

et al. 2022

Anticancer Res

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Section: Discussionmentioning

confidence: 99%

Oral-recombinant Methioninase in Combination With Rapamycin Eradicates Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model

Masaki¹,

Han²,

Samonte³

et al. 2022

Anticancer Res

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“…Previously we have shown that o-rMETase has potential clinical efficacy in prostate and pancreatic cancer patients (30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Long-term Stable Disease in a Rectal-cancer Patient Treated by Methionine Restriction With Oral Recombinant Methioninase and a Low-methionine Diet

et al. 2022

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Background/Aim: Rectal cancer is a recalcitrant disease with limited treatment options. Pre-clinical studies have shown the efficacy of methionine restriction with a lowmethionine diet and oral recombinant methioninase (o-rMETase) for colorectal cancer. There are also clinical studies on methionine restriction with o-rMETase for other recalcitrant cancer types. The goal of the present study was to determine the efficacy of a low-methionine diet and o-rMETase on a rectal cancer patient. Patient and Methods: A 55-year-old man diagnosed with recurrent locally-advanced rectal-cancer was treated with o-rMETase and a low-methionine diet, during which time, he did not receive standard chemotherapy. Disease stability was monitored by carcinoembryonic antigen (CEA) levels, sigmoidoscopy, and computed tomography (CT). Results: The patient was diagnosed with stage II rectal cancer (adenocarcinoma) in 2018. After neoadjuvant chemoradiotherapy, the patient received total mesorectal excision (TME) in 2018. Local recurrence was found by sigmoidoscopy one year later. The patient was given chemotherapy, the recurrent lesion shrunk, and was then removed endoscopically in December 2019, with positive margins. The tumor did not become apparent for about a year after that. An endoscopic examination performed in December 2020, revealed a local recurrence. Since that time, the patient had an elevated CEA. The patient went on o-rMETase and a low-methionine diet from January 2021. Since then, the patient's CEA level has remained stable for the next year and a half. He received sigmoidoscopy and CT regularly, and the tumor size has not changed. Conclusion: This patient's clinical course indicates that o-rMETase and a low-methionine diet may be effective for rectal cancer, for long-term disease stabilization. Further case studies and clinical trials are needed to determine the generality of the present result.Colorectal cancer is the fourth-most common cancer and the second leading cause of cancer death in the United States (1). Rectal cancer accounts for about one-third of these cases. Regarding locally-advanced disease (T3-4, N0), neoadjuvant chemoradiotherapy and adjuvant chemotherapy are the standard-of-care for rectal cancer. Although the 3-year diseasefree survival rate has increased from 62.9 % to 75.9 % for locally-advanced disease, it is still not sufficient (2-4). It is also important for patients with rectal cancer to preserve anal function. Most patients with rectal cancer, especially those whose tumor is located close to the anal verge, have undergone total mesorectal excision with a colostomy.Methionine addiction is a fundamental and general hallmark of cancer (5-7) and is termed the Hoffman effect (8). Since cancer cells require a greater amount of methionine than normal cells, which is due to the excess transmethylation reactions in cancer cells, they cannot survive under the condition of methionine restriction (9-11). We have developed recombinant methioninase (rMETase) (12), which catabolizes methionine, and have shown th...

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“…Oral METase has shown clinical promise in patients with prostate cancer (20)(21)(22), pancreatic cancer (23) and rectal cancer (24). No adverse effects have been reported, demonstrating its administration is acceptable to patients.…”

Section: Discussionmentioning

confidence: 99%

Elimination of Axillary-Lymph-Node Metastases in a Patient With Invasive Lobular Breast Cancer Treated by First-line Neo-adjuvant Chemotherapy Combined With Methionine Restriction

et al. 2022

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Background/Aim: Invasive lobular carcinoma (ILC) of the breast has a low complete-response rate in the neoadjuvant-chemotherapy setting. The addiction to methionine is a fundamental and ubiquitous characteristic of cancer cells, termed the Hoffman effect. We have previously targeted methionine addiction of breast cancer with recombinant methioninase (rMETase) using patient-derived orthotopic xenograft (PDOX) models. The aim of the present study was to determine the efficacy of methionine restriction with rMETase and a low-methionine diet combined with first-line neo-adjuvant chemotherapy, in a patient with metastatic ILC of the breast. Case Report: A 62-year-old female was diagnosed with metastatic ipsilateral axillary-lymph-node recurrence of breast ILC 3 years after mastectomy. The patient underwent [ 11 C]methionine positron-emission tomography (METPET) which showed extensive methionine accumulation in the ipsilateral axillary lymph nodes, indicating the presence of cancer cells. The patient received standard neo-adjuvant chemotherapy, which consisted of 3 months of doxorubicin and cyclophosphamide followed by 3 months of docetaxel from March 2022. The patient also went on a low-methionine diet and daily oral rMETase as a supplement every 6 hours concurrently with six months chemotherapy. The patient's blood carcinoembryonic antigen (CEA) level decreased gradually, and computed tomography findings showed loss of axillary lymph-node metastases in the first 3 months of neo-adjuvant chemotherapy with doxorubicin and cyclophosphamide combined with rMETase and a lowmethionine diet. Α complete response was demonstrated by METPET at 6 months, at conclusion of docetaxel chemotherapy. Conclusion: Combination therapy of doxorubicin and cyclophosphamide followed by docetaxel combined with methionine restriction led to a remarkable complete response that is expected in fewer than 10% of patients with ILC of the breast treated with neo-adjuvant chemotherapy alone. The present results suggest that methionine restriction in combination with doxorubicin and cyclophosphamide followed by docetaxel may be effective, after METPET has demonstrated the presence of methionine-addicted axillary-lymph-node metastases in ILC of the breast.Breast cancer is the most common cancer type and the second cause of death in females in the United States (1). Invasive breast cancer is a histologically heterogeneous disease with many histopathological subgroups. Invasive lobular carcinoma (ILC) is the second-most prevalent type of invasive breast cancer following invasive ductal carcinoma (IDC), accounting for 5% to 15% of all breast cancer cases (2). ILC is more likely to be hormone-positive, human epidermal-growthfactor-receptor-2 negative, and have a lower proliferative index compared to IDC. ILC has a lower complete response rate to neo-adjuvant chemotherapy but better recurrence-free and overall survival than IDC (2-4).

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Stage IV Pancreatic Cancer Patient Treated With FOLFIRINOX Combined With Oral Methioninase: A Highly-Rare Case With Long-term Stable Disease

Cited by 21 publications

References 0 publications

Oral-recombinant Methioninase in Combination With Rapamycin Eradicates Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model

Oral-recombinant Methioninase in Combination With Rapamycin Eradicates Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model

Long-term Stable Disease in a Rectal-cancer Patient Treated by Methionine Restriction With Oral Recombinant Methioninase and a Low-methionine Diet

Elimination of Axillary-Lymph-Node Metastases in a Patient With Invasive Lobular Breast Cancer Treated by First-line Neo-adjuvant Chemotherapy Combined With Methionine Restriction

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